We plan to carry out theoretical studies on the carcinostatic mechanisms using the molecular orbital theory as a tool. Our goal is to understand the anti-tumor activities of drug at the submolecular level. At first we will concentrate our efforts on the molecular complex formation between actinomycin D and DNA. Through direct selfconsistent field calculations and second order perturbation calculations we plan to obtain the stabilization energy and the charge transfer in a simplest model which consists of the actinomycin chromophore and a nucleic acid base. More complicated models including dinucleotides or hydrogen- bonded base pairs would also be examined. The effect of deviation from the experimentally observed geometry on the stability of the complex will also be studied. Furthermore the effect of hydrogen bonds between the base and the peptide sidechain of actinomycin and the effect of hydration will be elaborated. Various modifications of actinomycin D, some at the chromophore and some at the peptide sidechain will also be studied by molecular orbital method to find potentially more effective anti-tumor agents (drug design). Molecular orbital studies on other anti-tumor drugs will also be carried out. Mitomycin C, alkylating agents such as nitrogen mustards, and antimetabolites such as purine and pyrimidine analogues are to be included. For these compounds an effort is to be made to find relationships between the anti-tumor activity and some measure of reactivity or interaction energy. From such relationships one might propose a model of the carcinogenic mechanism and use it to design new drugs with a large potency. Finally studies on the relationship between carcinogenic mechanisms and carcinostatic mechanisms will be carried out by comparing proposed models and reactivity indices in both cases.